Differentiated thyroid cancer is a malignant tumour that has a fairly good prognosis, with patients surviving for many years. Multimodal therapy with surgery, radioiodine therapy and TSH suppressive medication is of proven efficacy. However, loss of differentiation is observed in up to one-third of patients with differentiated thyroid cancer, paralleled by an increase in tumour grading and loss of thyroid-specific functions (thyrotropin receptor, iodine accumulation). Such tumours may no longer be amenable to standard treatment protocols, including TSH suppression and radioiodide therapy. Retinoic acids have been shown to exert re-differentiating effects on thyrocytes in various experimental studies and case reports, and it was on this basis that this pilot study was initiated. Patients with advanced thyroid cancer and without the therapeutic options of operation or radioiodide therapy were treated with 13- cis-retinoic acid at a dosage of 1.5 mg/kg body weight daily over 5 weeks. Parameters for assessment of the therapeutic effect were serum thyroglobulin (TG) levels, radioiodine uptake, and tumour size prior to and after retinoid treatment. Fifty patients were evaluated for response, classified as reduction in tumour size and TG levels, stable disease or disease progression. Thirteen patients showed a clear increase in radioiodine uptake, and eight a mild increase. TG levels were unchanged or decreased in 20 patients. Tumour size was assessable in 37 patients; tumour regression was observed in six, and there was no change in 22. In total, a response was seen in 19 patients (38%). Response to retinoid therapy did not always correlate with increased radioiodine uptake, so other direct antiproliferative effects have to be assumed. The encouraging results of the study and the low rate of side-effects with good tolerability of retinoids warrant further studies with altered inclusion criteria and employment of other redifferentiating drugs or combinations of agents.

The aim of this study was to evaluate the clinical use of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in medullary thyroid cancer (MTC) on the basis of comparison with findings obtained using indium-111 pentetreotide (SMS), pentavalent technetium-99m dimercaptosuccinic acid (DMSA), technetium-99m sestamibi (MIBI), computed tomography (CT) and magnetic resonance imaging (MRI). One hundred FDG-PET examinations in 85 patients (40 males, 45 females) with elevated tumour marker levels and/or pathological findings on other imaging methods were evaluated retrospectively. Eighty-two patients were examined after total thyroidectomy, and the remaining three patients prior to surgery. Overall, 181 lesions could be identified with at least one of the imaging techniques. Fifty-five lesions were confirmed histologically. FDG-PET detected 123 of 181 sites, which is a lesion detection probability of 68%. In the 55 cases with histological confirmation, we found 32 true positive, 3 false positive, 11 true negative and 9 false negative lesions using FDG-PET, resulting in a sensitivity of 78% and a specificity of 79%. Sensitivity and specificity were, respectively, 25% and 92% for SMS, 33% and 78% for DMSA, 25% and 100% for MIBI, 50% and 20% for CT and 82% and 67% for MRI. Compared with morphological techniques and functional imaging methods with single-photon emitters, FDG-PET showed the highest lesion detection probability for MTC tissue, with a high sensitivity and specificity. It is concluded that FDG-PET is a useful method in the staging and follow-up of MTC.

There is controversy over the factors that may influence the outcome of radioiodine therapy for benign thyroid diseases. Antithyroid medication has been claimed to negatively influence the effectiveness of radioiodine therapy in Graves' disease. In a longitudinal study, we assessed the influence of sex, age, antithyroid drugs, target radiation dose, target mass, applied activity, delivered dose, interval between last meal and application, and TSH, FT3 and FT4 levels on the outcome of radioiodine therapy. One hundred and forty-four patients (111 female, 33 male) suffering from Graves' disease (GD) and 563 patients (434 female, 129 male) with toxic nodular goitre (TNG) were entered in the study and followed up until 8 months after therapy. Treatment was defined as successful when the TSH level was found to be normal or elevated. Ninety-eight GD patients and 418 TNG patients were successfully treated. Forward stepwise multiple regression analysis models retained only the target mass in GD and the applied activity in TNG as significantly associated with the outcome of therapy. The predictive value of all variables involved was extremely low in both disease groups. Whereas concomitant antithyroid medication had no influence in GD, it adversely influenced radioiodine therapy of TNG. This effect may be attributed to a radioiodine "steal phenomenon" induced by TSH-stimulated normal thyroid tissue, which causes overestimation of the uptake in toxic nodules.

No abstract

Tbe benzodiazepines are a class of d.rugs that are widely used in the treatment of various psychiatric disorders. One member of um ~' oxazepam, is also a common metabolite of sevmd other benzod.iazepines. Since the evidence for the genetic toxicity and carcinogenic properties of these compounds is incol:lsb1ent, we investigated the oxazepam-induced fonnation of micronuclei in Syrian Hamster embryo fibroblast (SHE) cells, human amniotic fluid fibroblast-like (AFFL) cells and LS178Y mouse cells. A dose-dependent increase in micronucleus fractions was found in all tbree ceU llnes. The time course of micronucleus induction in L5178Y cells showed a maximum at 5 h after treatment, suggesting that the micronuclei were fonned in the first mitosis after treatment.Kinetochore staining (CREST -antiserum) revealed the presence of kinetochores in -SO% of the micronuclei in aU tbree ceU types. ThJs resu1t was further confinned by in situ bybridization in LS178Y cells and indicates tbe presence of wbole Chromosomes or centric fragments as weU as acentric fragments in the oxazepam-induced micronuclei. The LS178Y cells did not show a mutagenic response to oxazepam at any of the doses or expression times used.